Management of Biliary Strictures After Liver biliary strictures after liver transplant was reported
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316 Gastroenterology & Hepatology Volume 11, Issue 5 May 2015
Management of Biliary Strictures After Liver Transplantation Nicolas A. Villa, MD, and M. Edwyn Harrison, MD
Keywords Anastomotic strictures, nonanastomotic strictures, endoscopic retrograde cholangiography, deceased donor liver transplant, living donor liver transplant, biliary stenting, biliary dilation
Dr Villa is an advanced endoscopy fellow and Dr Harrison is a professor in the Divi- sion of Gastroenterology and Hepatology at the Mayo Clinic in Scottsdale, Arizona.
Address correspondence to: Dr M. Edwyn Harrison 13400 East Shea Boulevard Scottsdale, AZ 85259 Tel: 480-301-4914 E-mail: Harrison.M@mayo.edu
Abstract: Strictures of the bile duct are a well-recognized compli-
cation of liver transplant and account for more than 50% of all
biliary complications after deceased donor liver transplant and
living donor liver transplant. Biliary strictures that develop after
transplant are classified as anastomotic strictures or nonanasto-
motic strictures, depending on their location in the bile duct. The
incidence, etiology, natural history, and response to therapy of the
2 types vary greatly, so their distinction is clinically important. The
imaging modality of choice for the diagnosis of biliary strictures is
magnetic resonance cholangiopancreatography because of its high
rate of diagnostic accuracy and limited risk of complications. Bili-
ary strictures that develop after liver transplant may be managed
with endoscopic retrograde cholangiography (ERC), percutaneous
transhepatic cholangiography (PTC), or surgical revision, includ-
ing retransplant. The initial treatment of choice for these strictures
is ERC with progressive balloon dilation and the placement of
increasing numbers of plastic stents. PTC and surgery are gener-
ally reserved for failures of endoscopic therapy or for anatomic
variants that are not suitable for ERC. In this article, we discuss
the classification of biliary strictures, their diagnosis, and the
therapeutic strategies that can be used to manage these common
complications of liver transplant.
Biliary strictures are a well-known and common complication of both living donor liver transplant (LDLT) and deceased donor liver transplant (DDLT) and account for more than 50% of all biliary complications of liver transplant.1-3 The factors that most commonly contribute to stricture formation include the surgical reconstruction technique (eg, duct-to-duct anastomosis vs choledochojejunostomy), use of a T-tube, type of liver transplant procedure (LDLTs are more prone to strictures than DDLTs), and development of hepatic arterial thrombosis. Biliary strictures are classified as anastomotic strictures or nonanastomotic strictures, depending on their location.
Gastroenterology & Hepatology Volume 11, Issue 5 May 2015 317
M A N A G E M E N T O F B I L I A R Y S T R I C T U R E S A F T E R L I V E R T R A N S P L A N T A T I O N
In the early surgical experience, the incidence of biliary strictures after liver transplant was reported to be as high as 60%.4 With improvements in organ selection, retrieval, and preservation as well as the standardization of biliary reconstruction techniques, the incidence of bili- ary strictures has been reduced dramatically to less than 16% overall.5-8 In a meta-analysis involving more than 14,000 patients, the incidence of anastomotic strictures was reported to be approximately 13%.9 The incidence of nonanastomotic strictures is considerably lower (4%-10% in 2 studies).8,10
Biliary strictures can occur months to years after liver transplant, but they most commonly present within the first year, with a mean interval from transplant to time of presentation of 5 to 8 months.11-13 Strictures that occur early after liver transplant usually result from technical problems in the surgery itself, whereas strictures that develop later arise mainly from vascular insufficiency, immunologic causes, or problems with healing and fibrosis.14-16
Although biliary strictures account for significant morbidity and mortality after liver transplant, advances in endoscopic therapy and interventional radiology have improved outcomes by decreasing the need for surgical repair or retransplant, both of which carry much higher morbidity and mortality rates. Currently, the first line of treatment for biliary strictures is endoscopic therapy. In this article, we discuss the classification of biliary stric- tures, their diagnosis, and the strategies used to treat them.
Biliary strictures are classified as anastomotic or nonanas- tomotic, depending on their location. Their incidence, etiology, natural history, and response to therapy differ greatly, so the distinction between the 2 types of strictures is clinically important.
Anastomotic Strictures Anastomotic strictures are defined as segmental or focal narrowings around a biliary anastomosis and are thought to result primarily from fibrotic healing (Figure 1).17 Anastomotic strictures are more common than nonanas- tomotic strictures, are localized at the site of anastomosis, and are single, focal, and short.1,18,19
Before the 1990s, anastomotic strictures affected approximately a third of patients.4,19,20 With the advent of improved techniques, the overall incidence of anas- tomotic strictures is reported to be approximately 13%; strictures at the biliary anastomosis develop after DDLT in 12% of patients (range, 5%-15%) and following LDLT in 19% (range, 13%-36%).9,12,21-24 The higher incidence of strictures after LDLT is explained by the necessity for resecting a portion of the donor liver rather than using the entire organ, as is possible with DDLT. With resection of the donor graft in LDLT, there is a risk of devasculariza- tion of the bile duct at the hilar dissection and the poten- tial for bile leakage from the cut surface, causing fibrotic changes around the anastomosis. The use of a partial liver for the graft also frequently results in the requirement for multiple anastomoses of smaller bile ducts.25-27
The onset of anastomotic strictures ranges widely, with strictures diagnosed from 7 days to 11 years after transplant, according to a meta-analysis.9 Although anas- tomotic strictures can present at widely variable times, the
Figure 1. Cholangiograms of anastomotic strictures in a deceased donor liver transplant (arrow, A) and a living donor liver transplant (arrows, B).
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V I L L A A N D H A R R I S O N
majority occur within the first year after transplant.6,11,19 However, it also appears that the incidence increases with longer follow-up, as the cumulative risk of anastomotic strictures at 1, 5, and 10 years after transplant is 6.6%, 10.6%, and 12.3%, respectively.18
Risk factors associated with the development of anas- tomotic strictures are numerous and include recipient, graft, operative, and postoperative factors. The contribu- tions of these risk factors differ between patients undergo- ing DDLT and those undergoing LDLT (Table). The most common risk factors for anastomotic strictures in patients undergoing DDLT are advanced recipient age, female donor, failure to flush the donor duct, preceding bile leakage, acute rejection, chronic rejection, and choledo- chojejunostomy or hepaticojejunostomy reconstruction rather than duct-to-duct reconstruction.18,19,28-31 The most common risk factors for anastomotic strictures in LDLT are advanced recipient age, advanced donor age, more than 1 biliary anastomosis, longer cold and warm ischemia times, preceding bile leakage, hepatic artery thrombosis, and duct-to-duct reconstruction rather than hepatico- jejunostomy reconstruction.23,32-39 Technical issues may be responsible for anastomotic strictures in both DDLTs and LDLTs, including improper surgical technique, small caliber of the bile ducts, inappropriate suture material, and tension at the anastomosis.40 As a general rule, anastomotic strictures that appear early in the postoperative period are usually secondary to surgical technical issues or postopera- tive bile leak, whereas those that appear later are most likely due to fibrotic healing arising from ischemia at the end of the donor or recipient bile duct.13,15,18
Nonanastomotic Strictures A nonanastomotic stricture is defined as 1 or more focal areas of narrowing of the bile ducts proximal to a biliary anastomosis,11,12 and often occurs at multiple sites. These strictures are longer and occur less frequently and earlier than anastomotic strictures, with a mean time to stricture formation of 3 to 6 months.8,10,12 The overall incidence of nonanastomotic strictures has been reported to be from 4% to 10%.8,10 It is thought that these strictures develop as a result of ischemia and immunologic events. The pri-
mary risk factors for ischemic strictures include hepatic artery thrombosis, chronic ductopenic rejection, blood type ABO incompatibility, and a diagnosis of primary sclerosing cholangitis before transplant.5,10,41,42 Studies also have suggested that a pretransplant diagnosis of auto- immune hepatitis, prolonged warm and cold ischemia times, donation after cardiac death, and prolonged donor use of vasopressors are independent risk factors for non- anastomotic stricture formation.10,43,44
Nonanastomotic strictures are commonly associated with secondary problems. Because of the presence of